We are actively studying the regulation of intracellular enzyme level as a possible mechanism of protein turnover and aging. We have previously characterized the degradation of Escherichia coli glutamine synthetase (GS) and have presented evidence for a two-step process involving inactivation followed by proteolysis. Furthermore, we have characterized several enzymic mixed-function oxidation systems which catalyze inactivation of GS and one of these systems, a cytochrome P-450 system purified from rabbit liver microsomes, has recently been studied in considerable detail. The generality of the oxidative inactivation reaction is supported by the demonstration that several key metabolic enzymes other than GS are inactivated in a qualitatively similar manner by at least two enzymic mixed-function oxidation systems, namely, microbial NADH-oxidase and the cytochrome P-450 systems. Furthermore, several enzymes which we have found to be inactivated by the mixed-function oxidation systems have been found by others to accumulate in an inactive or less active form during aging. As an extension of these studies we are also investigating this type of enzyme inactivation in bacteria by activated neutrophils as a possible mechanism of bacterial cell killing. We have been able to demonstrate inactivation of exogenous GS as well as GS in whole intact E. coli by activated neutrophils.